GLUCOSE-INDUCED INTRACELLULAR ION CHANGES IN SUGAR-SENSITIVE HYPOTHALAMIC NEURONS

In the lateral hypothalamic area (LHA) of rat brain, similar to 30% of cells showed sensitivity to small changes in local concentrations of glucose. These ''glucose-sensitive'' neurons demonstrated four types o f behavior, three of which probably represent segments of a continuous spectrum of recruitment in response to ever more severe changes in bl ood sugar. Type I cells showed maximum activity less than or equal to 5.6 mM blood glucose but became completely silent at hyperglycemia of 10-12 mM (normoglycemia 7.6 +/- 0.3 mM; mean +/- SD). Type II and In n eurons exhibited a wider range of response. Type IV cells (5-7% of glu cose-sensitive neurons) paralleled the behavior of sugar-sensitive cel ls in ventromedial hypothalamic nucleus (VMH). In VMH, similar to 40% of cells responded to changes in blood glucose over a range of concent rations from 3.6 to 17 mM, by increasing their firing rate as sugar le vel rose and vice versa. Ionic shifts during increases in blood (brain ) glucose levels were similar in LHA types I-III but fastest in I and slowest in III. [Na+](i) fell by 5-9 mM, [K+](i) rose by 6-8 mM, and p lasma membrane hyperpolarized by 5 mV. [Ca2+](i) declined by 15-20 nM in line with membrane hyperpolarization. In VMH and type IV LHA cells, [K+](i) fell 3-8 mM and plasma membrane depolarized -3 to -5 mV as bl ood/brain glucose concentration increased from 7.6/2.4 to 17.6/4.2 mM, whereas [Ca2+](i) increased from 125 to 180 nM as a consequence of fa lling membrane potential. During falls in blood/brain sugar concentrat ion the effects in both VMH and LHA cells were reversed. The findings are consistent with the ionic shifts in types I-III LHA cells being de pendent on alterations in Na/K-ATPase activity, whereas those in VMH a nd type IV LHA cells could be caused by modulation of ATP-dependent K channels. A possible mechanism for linking the effects of small chang es in glucose to ATP generation, which could bring about the above phe nomena, is the interposition of a ''glucokinase-type'' enzyme in a rol e similar to that which it has in glucose-sensing pancreatic beta-cell s.